Applicants reported in the Journal of Medicinal Chemistry, 1979, Vol. 22 at pages 855 and 1367 on a series of thiosemicarbazones derived from 2-acetylpyridine which possess significant antimalarial activity. The molecular features which have been shown to be essential for antimalarial activity are the presence of a 2-pyridylalkylidene moiety, an attached thiocarbonyl or selenocarbonyl group (in contrast to a carbonyl group) as reported in Eur. J. Med. Chem., 1981, Vol. 16, page 317, and the presence of certain bulky substituents at position N.sup.4.
In view of the electronic similarity of selenium to sulfur, applicants decided to test selenium analogs of two of the more active antimalarial compounds, namely, N-[4-(2-pyridyl)piperazine]-2-[1-(2-pyridyl)ethylidene]hydrazinecarbothioa mide (compound 1) and N-(2-,6-dimethylmorpholine)-2-[-(2-pyridyl)ethylidene]hydrazinecarbothioam ide (compound 2). Whereas ##STR1## compound 1 had diminished antimalarial activity relative to its sulfur analog, compound 2 had antimalarial activity comparable to its sulfur analog with surprisingly lower toxicity.
In view of these considerations, applicants decided to prepare 2-acetyl- and 2-propionylpyridine selenosemicarbazones in order to investigate their antimalarial and antileukemic properties.